Cracking the Foundations - The Pacific Fatigue Lab and Chronic fatigue Syndrome (ME/CFS)
Phoenix Rising: An ME/CFS/FM Newsletter (Jan 09) by Cort Johnson
(Click here to download a Pdf
File of 'Cracking the Foundations')
Could a small lab in the Central Valley of California shake the CFS research
field with a quake of epic proportions? Change how the disease is viewed? How
it’s defined? Legitimize the disease once and for all? It’s possible that given
enough resources the Pacific Fatigue Lab at the University of the Pacific in
Stockton, California may do all of these.
Run by three exercise physiologists, Dr. Christopher. Snell (Ph.D), Dr. MarkVan
Ness (Ph.D) and Staci Stevens (M.A.), a former grad student and now a researcher
with chronic fatigue syndrome (ME/CFS), the lab focuses on a very basic and
still very misunderstood aspect of CFS – why patients have so much trouble with
exercise.
Staci Stevens, the founding Executive Director of the Pacific Fatigue Lab
explained. “Many researchers look at ME/CFS patients when they’re at rest- at
baseline. But as any ME/CFS patient knows, the real problems occur when their
systems are under stress due to too much activity. We’re taking a close look the
physiology of CFS patients as they undertake the most stressful activity of all
– exercise.”
Since oxygen plays a key role in energy production, exercise physiologists use
oxygen consumption during exercise to tell how much energy a person’s body is
capable of producing. Having people pedal a stationary bicycle until they can
pedal no more tells researchers how much air their lungs can take in
(Ventilation Max) and therefore how much oxygen they use to produce energy (VO2
Max) at their peak level of effort. Since oxygen plays a key role in the energy
production process this test effectively tells researchers how much energy is
being produced.
Given the fatigue and post-exertional problems often noted in ME/CFS one would
think aerobic exercise tests would have played a key role in legitimizing this
disease, but instead they’ve given rise to further skepticism. The ability of
many patients to pass them has added to confusion about a disease characterized
by the word fatigue. How could CFS patients be so fatigued if they’re able to
generate normal amounts of energy?
A New Approach. The Pacific Fatigue Lab researchers realized, however, that while researchers
may have been asking the right questions they were asking them in the wrong way.
Many ME/CFS patients can, after all, get through a single ‘workout’ or a single
day or single afternoon at work okay only to ‘crash’ afterwords. Until now,
though, no one’s taken a close look at the ME/CFS patient’s ability to produce
energy when they’re in a crash – an odd oversight in a disease whose symptoms
are so tied to activity. (Indeed, study after study is showing that many
variables which test out normal or near normal when ME/CFS patients are at rest
are abnormal when their systems are put under stress). With the Pacific Fatigue
Lab doing a new exercise testing regime, two exercise tests two days in a row
and other tests (now known as the Stevens’ Protocol) they’ve given the
post-exertional problems ME/CFS patients have reported for so many years a
chance to show up – and they have.
Their results are both profound and disturbing. About half of the ME/CFS
patients they’ve tested do, in fact, ‘fail’ or significantly under perform in
the first single exercise test – they cannot generate normal amounts of energy
even when they’re ‘rested’. It’s the rest of the patients that are so
intriguing, though. When you give these patients a second test a day later many
of them will fail as well--and fail spectacularly.
The amount of impairment the Lab see’s can be astonishing - some patients suffer
as much as a 50% drop in their ability to produce energy the next day. Ms.
Stevens spoke of a twenty-something man whose next day exercise tests were worse
that those of a normal 85 year old. In a hospital setting his cardiopulmonary
exercise profile would suggest he had heart failure.
Revolutionary Findings - According to modern medical science this shouldn’t occur. For decades
researchers have shown that human beings, under virtually all conditions and in
a variety of disease states, can take an exercise test to exhaustion, recover
and return the next day and score the same the next day. It doesn’t matter if
she/he has heart failure or end-stage kidney disease – again and again
researchers have shown that the human body – even in extremely poor health - has
an amazing ability to quickly return to a baseline level of energy. That is
until now.
But it’s not just that chronic fatigue syndrome (ME/CFS) patients are failing
these tests, it’s also the unique way they’re failing them that’s raising
eyebrows. Decades of research have shown if you a take a female of W age and
have her do X amount of exercise at Y heart rate she will exhibit Z levels of
oxygen consumption. Researchers have believed these algorithms are set in stone
but they’re not holding up in chronic fatigue syndrome (ME/CFS) patients. That
they’re not suggests that something has gone awry in the basic physiological
processes the body uses to produce energy in this disease.
Even after 20 years in the field Staci Stevens’ excitement was palpable. The
implications of her findings are profound not just for ME/CFS patients but for
the field of exercise physiology. She said “We are charting waters that have
never been charted before. It’s an exciting time to be involved in CFS
research!”
The lab’s findings are so unusual that their peers
sometimes can’t believe what they’re hearing. Since decades of research have
indicated there’s no need to do repeat exercise tests, they are simply not done.
Until recently the Pacific Fatigue Lab may be the only lab in the world that
regularly does them. I asked Staci Stevens how her colleagues across the country were reacting to
this data – were they excited? She said some of them say, “It’s just not
possible, they think we must have imputed the data wrong but others are
enthralled”. She said one colleague on the east coast who’s doing the tests said
that after 30 years in the field, “I’d never seen anything like this”.
A Quick Road To Legitimacy? – Their findings undermine long held beliefs not
only about chronic fatigue syndrome (ME/CFS) but about exercise physiology as
well. Overturning paradigms is not easy but the Pacific Fatigue Lab has an ace
in the hole in this regard. Many ME/CFS researchers and patients have looked to
the future for technological breakthroughs that will legitimize the disease once
and for all. The new technologies coming to bear on ME/CFS are exciting but new
technologies take time, sometimes long periods of time, to be assimilated and
accepted.
There’s nothing new, however, about the technology the Lab is using; in fact
it’s boringly well established. The aerobic exercise tests they do form an
essential part of every cardiologist’s and pulmonologist’s tool kit. Once the
Pacific Fatigue Lab’s test results are replicated and make it into the broader
research community acceptance should come relatively quickly. In fact if one
were to chart the quickest road to legitimacy for this disease it would very
much look like the path the Pacific Fatigue Lab has embarked on - charting gross
abnormalities in well accepted, well established tests. If the Pacific Fatigue
Lab’s findings hold up, the news couldn’t be better for chronic fatigue syndrome
(ME/CFS) patients.
Redefining Chronic Fatigue Syndrome (ME/CFS) – The Pacific Fatigue Lab’s results
should also clarify one of the key questions concerning the disease: whether
researchers have been mixing apples and oranges in their studies. For decades
researchers have worried that the disease’s vague definition allows people with
different illnesses to participate in research studies. The most pressing
question concerns whether ‘post-exertional malaise’ (PEM), which signifies
dramatically worsening symptoms after physical or mental exertion, uniquely
identifies this disorder or is simply one symptom among many.
One side, lead by the producers of the Canadian Consensus Definition of ME/CFS,
believes that post-exertional malaise (PEM) is a hallmark symptom that reflects
unique physiological processes. They believe that allowing people without this
problem to participate in chronic fatigue syndrome (ME/CFS) studies may have
greatly hampered efforts to understand this disease.
The other side, exemplified in the Center for Disease Control’s (CDC) empirical
definition of 2005, believes that post-exertional malaise (PEM) is one of many
symptoms present in the disease. They argue that the most important feature of
the disease is unexplained degrees of ‘unwellness’ that interfere significantly
with people’s work, personal, social, etc. activities. They believe some
different process is at work.
The Pacific Fatigue Lab’s results suggest that the Canadian Consensus group is
correct; during either the first or second exercise test a large subset of
patients demonstrates significant physiological abnormalities in their ability
to produce energy. Another subset of patients does not. The Lab’s findings
suggest that these two groups should be separated in research studies.
Ms. Stevens could not say, however, how big the PEM subset is. The Lab has
derived most of its data from three groups of patients – research subjects in
the test/ re-test studies, those attempting to get disability and participants
in the Ampligen trials. Many of the people they screen do exhibit PEM on the
exercise tests but others do not. It will take statistically rigorous studies to
determine how prevalent the post-exertional malaise group is.
Demonstrating that this subset does exist and can be differentiated by standard
physiological tests would go a long way toward breaking up the CFS label,
revamping the definition of the disease, focusing researchers in on key
abnormalities, and, of course, creating a new name.
Answering the subset question would be tremendously valuable but the Stevens’
Protocol could also have an enormous impact on another very bread and butter
issue: disability.
A Comprehensive Disability Evaluation – CDC studies indicate that the average
annual financial costs of CFS (@$25,000/year) impose an economic burden that
many families cannot sustain for long. Getting disability can be the difference
between absolute poverty and at least a minimum amount of financial comfort and
medical attention. Without clear diagnostic or functional tests, however,
getting disability has been a challenge.
Chronic fatigue syndrome (ME/CFS) patients don’t win their disability cases
because they have ME/CFS, they win when they can demonstrate they cannot
function well enough to work. Fortunately, measuring functioning is what the
Pacific Fatigue Lab is all about. The simplicity of the exercise tests is their
grace; patients who cannot produce sufficient amounts of energy cannot be
expected to function – it’s as simple as that. Aerobic exercise tests have the
added advantage of a long history; they’ve been used to demonstrate disability
in heart patients and others for decades. The Steven’s Protocol has the
potential to produce a clarity that has been strikingly missing in this arena.
The Pacific Fatigue Lab offers perhaps the most extensive disability evaluation
in the country. The exercise tests don’t take long – 8-10 minutes with a slow
windup period. – and they can have brutal after-effects– but, if successful,
they are time well spent. (The Pacific Fatigue Lab will not allow severely
disabled patients or those with moderate to high cardiovascular risk to take the
tests. If the first test shows disability the next test is not needed).
To schedule a disability evaluation contact Staci Stevens at (209) 946-7649 or email: sstevens@pacific.edu
They’re not cheap, but even at $2,000 a pop, they present a good value for those
who can afford it. (Single exercise tests typically run from $800-$1200 at a
hospital. Some insurance companies will reimburse for the testing though billing
insurance is the responsibility of the client). The Stevens’ Protocol 8-12
minute aerobic exercise tests, resting pulmonary function tests measuring lung
function, bioelectrical impedance exams measuring hydration, acoustic nasal
rhinometry measuring sympathetic nervous system functioning, reaction time
testing evaluating cognitive processing time, and a seven page written
evaluation. Not every patient who does the disability evaluation gets a
diagnosis of ‘disabled,’ but for those who do it can be financial lifesaver.
The Stevens’ Protocol has the potential to rewrite the disability rules for
ME/CFS. The CFIDS Association of America has already asked the Social Security
Administration to take them into account but they’re behind the game; the
Fatigue Lab has already notched its first of several wins in the long term
disability field. In fact, their first win holds a place of honor in a frame on
the wall of their office.
Education With all the many ramifications of the Lab’s work, it’s the day to
day process of educating students about ME/CFS that may be the most fulfilling
for Staci. She, Dr. VanNess and Dr. Snell all incorporate their latest findings
into their classes; ‘Here is a normal exercise stress test’ they say and ‘here
is a CFS patient’s’ test. The students are enthralled and they should be; they
are being exposed to cutting edge data that the textbooks say shouldn’t be
happening. It’s exciting to be a young (or old) student on the cusp of research
that has the possibility of overturning accepted paradigms. Ms. Stevens laughed
and said “They love working with CFS patients. They’re always asking to see the
results on the last patient”.
When these students leave the University of the Pacific they’ll be ambassadors
for this disease and spread the word about the unusual findings. Currently the
PFL has four graduate students and a handful of undergraduates working with
them.
They also provide hope for a field that is not attracting many new faces. In
fact, the lack of young researchers may be the biggest long-term problem the
research field faces. The researchers that got engaged in the field when it was
new and not subject to so much controversy will be retiring in the not so
distant future. Ms. Stevens lamented the lack of young faces at the Symposium on
Viruses in CFS in Baltimore in May, 2008.
The chronic fatigue syndrome (ME/CFS) research world is catching onto the
implications of the Pacific Fatigue Lab’s work. A repeat exercise study by Ellie
Stein in Canada recently opened and one is reportedly underway in Europe. Ms.
Stevens readily acknowledged that replicating results has been difficult in
ME/CFS, but she’s confident that their results will hold up. She’s done 1,000’s
of single cardiopulmonary exercise tests on chronic fatigue syndrome (ME/CFS)
over the years and close to a hundred with the Stevens’ Protocol at the Pacific
Fatigue Lab. Whether in Stockton, Stanford, Incline Village or Ithaca, New York
they see the same general pattern again and again, a unique metabolic
dysfunction that characterizes and objectifies the most mystifying symptom in
the disease, post exertional malaise.
(Research, education, treatment…does this sound familiar? Advocates have been
asking for the federal government to produce Centers of Excellence that combine
research, treatment and education. The Pacific Fatigue Lab is a COE in
miniature. )
Opportunity – The Pacific Fatigue Lab is a remarkable accomplishment – a
testament to one grad student’s persistence – and a small coterie of advisors
and mentors who made her passion their own. University affiliated chronic
fatigue syndrome facilities are almost non-existent. Aside from the
Whittemore-Peterson Neuro-Immune Institute in Reno, Nevada (which won’t open its
doors on the university campus for another two years) there may be no other
University sponsored Chronic Fatigue Syndrome lab in the country. Special thanks
must go to the Sport Sciences Department Chair Dr. Christopher Snell and to the
University of the Pacific for having the vision to recognize the opportunity the
Lab presents and backing it despite of the controversy still surrounding this
disease.
The opportunities the Lab presents for this disease are staggering. Yet the
contrast between the opportunity present and the resources available is a little
heartbreaking.
The Pacific Fatigue Lab is entirely volunteer run by three people who are trying
to analyze their data, get grants and publish on their off-time. Somehow,
they’ve managed to create a beautiful lab but they’re still missing key
ingredients. Their papers have mostly been published in less well known
journals, they don’t have a website to get the word out, and they don’t have a
strong funding base. Indeed the theme of overworked (and unpaid) researchers
trying to make do on a shoestring is a constant one in the ME/CFS research
community.
I asked Staci Stevens about doing heart rate variability (HRV) studies. Given
their ability to provide data on how the autonomic nervous system is functioning
–which appears to be a key player in the disease – HRV studies seem like a
perfect fit for the lab. She said ‘I’d love to do HRV but we don’t have the
funding’. Staci noted that “This doesn’t need to be rocket science. We could go
a long way just by focusing on some simple areas that the research community has
basically ignored” One gets the idea that there are many things the Pacific
Fatigue Lab could do to advance the science of ME/CFS if they just had a bit
more money.
But there’s only so much money and so much time in the day. The Pacific Fatigue
Lab has been able to produce what it has through two private grants from the
CFIDS Association of America and from funds it gathers from doing its
comprehensive disability studies and firefighter fitness testing on the side.
Currently the Lab’s researchers are focused on analyzing the results from the
Stanford Montoya Valcyte study and the data from their latest repeat exercise
study plus a new study, all while they’re teaching full loads
The Next Level One wonders what these researchers could achieve if they had
more time and money to focus on a subject that they’re obviously so passionate
about.
I asked Staci how much money would it take to move the Lab to next level? She
said ‘For sixty thousand dollars we could hire a Ph.D in exercise physiology to
write grants, run the studies and write up the data. There are plenty of people
who would love to get a job to do that”. Hiring a full time clinical testing
supervisor who could take over the grunt work of data input would allow them to
focus more on the big picture. Monetarily speaking this is chicken feed in the
medical world; they’re not far at all from creating a lab that could start
turning out study after study.
Ms. Stevens was reluctant to delve into the thorny issue of federal financing
for CFS research but it was clear that she felt that whatever semblance of a
spigot that had once been turned on has been mostly turned off. The loss of the
Cooperative Research Centers at the NIH in 2002 was a severe blow. The Pacific
Fatigue Lab’s efforts to get an NIH grant failed. When I asked if the Centers
for Disease Control had shown an interest in her work she said ‘Interest and
funding are two different matters and they are struggling with funding as well.’
One would think that somewhere in a community of 1,000,000 patients a way could
be found to assist them in their work.
Having a University support an ME/CFS laboratory is a rare thing. In fact, aside
from the Whittemore-Peterson Institute there doesn't appear to be another
University laboratory devoted to ME/CFS in the U.S. The
University of the Pacific deserves our heartfelt thanks for their leadership in
this area. Let's help out the PFL in their work. Please e-mail the people below and say
Thank You!
- Thomas W. Krise, Ph.D., Dean of the College of the Pacific:
email: tkrise@pacific.edu
- Edith Sparks, Ph.D., Senior Associate Dean: email: esparks@pacific.edu
- Jin Gong, Ph.D., Dean of Graduate Studies: email: jgong@pacific.edu
Advocacy When the federal system fails to assist people in need one must turn
to advocates to put pressure on the government. Ms. Stevens agreed that advocacy
was critical but noted that the problems with exhaustion chronic fatigue
syndrome (ME/CFS) patients faced made them ill-equipped for advocacy. Still she
noted that when she served on the federal advisory committee for CFS (CFSAC)
they typically had less than 5 patients show up for the meetings – and they
tended to be the same five patients - not a strong signal to the government to
move on these issues.
The Future - The Pacific Fatigue Lab is creating a body of work that has the
potential to revolutionize the medical community’s understanding of this
disease. The possibilities are impressive; legitimize ME/CFS, rewrite the
disease’s disability rules, create viable subsets, focus the attention of the
research community on the post-exertional period to determine how this disease
is defined and guide both non-pharmacological and pharmacological treatment to
improve quality of life for patients.
How well it will be able to achieve these goals will in good part depend on the
resources it has and how well it can get the word out about its findings. Indeed
the Lab is still mostly a secret in the ME/CFS community. Ms. Stevens said that
as they’ve been accumulating data and analyzing it that “We’ve been kind of
underground” but she also felt it was about time for them to come out. Chronic
fatigue syndrome (ME/CFS) patients can only hope they come out in a big way
indeed.
________________________________________
The Pacific Fatigue Lab is found at the University of the Pacific: 3601 Pacific Avenue,
Stockton, CA 95211; (209) 946-7649. email: sstevens@pacific.edu
Contribute to the Pacific Fatigue Lab through the Workwell Foundation; a
non-profit foundation created by Staci Stevens to advance research into chronic
fatigue syndrome (ME/CFS). Phone: (209)599-7194. email:
staci@workwellfoundation.org. Address: The Workwell Foundation, 601 Madsen Dr. Ripon, CA 95366
____________________